| Superoxide dismutase restores eNOS expression and function in resistance pulmonary arteries from neonatal lambs with persistent pulmonary hypertension. | |
| | |
MedLine Citation:
|
PMID: 18790993 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Endothelial nitric oxide (NO) synthase (eNOS) expression and activity are decreased in fetal lambs with persistent pulmonary hypertension (PPHN). We sought to determine the impact of mechanical ventilation with O(2) with or without inhaled NO (iNO) or recombinant human SOD (rhSOD) on eNOS in the ductal ligation model of PPHN. PPHN lambs and age-matched controls were ventilated with 100% O(2) for 24 h alone or combined with 20 ppm iNO continuously or a single dose of rhSOD (5 mg/kg) given intratracheally at delivery. In 1-day spontaneously breathing lambs, eNOS expression in resistance pulmonary arteries increased relative to fetal levels. eNOS expression increased in control lambs ventilated with 100% O(2), but not in PPHN lambs. Addition of iNO or rhSOD increased eNOS expression and decreased generation of reactive oxygen species (ROS) in PPHN lambs relative to those ventilated with 100% O(2) alone. However, only rhSOD restored eNOS function, increased tetrahydrobiopterin (BH(4)), a critical cofactor for eNOS function, and restored GTP cyclohydrolase I expression in isolated vessels and lungs from PPHN lambs. These data suggest that ventilation of PPHN lambs with 100% O(2) increases ROS production, blunts postnatal increases in eNOS expression, and decreases available BH(4) in PPHN lambs. Although the addition of iNO or rhSOD diminished ROS production and increased eNOS expression, only rhSOD improved eNOS function and levels of available BH(4). Thus therapies designed to decrease oxidative stress and restore eNOS coupling, such as rhSOD, may prove useful in the treatment of PPHN in newborn infants. |
| | |
Authors:
|
Kathryn N Farrow; Satyan Lakshminrusimha; William J Reda; Stephen Wedgwood; Lyubov Czech; Sylvia F Gugino; Jonathan M Davis; James A Russell; Robin H Steinhorn |
Related Documents
:
|
8882283 - Nutrient partitioning and fetal growth in rapidly growing adolescent ewes. 14744943 - Stereoselective pharmacokinetics of fluoxetine and norfluoxetine enantiomers in pregnan... 2792543 - Intra-uterine growth retardation is associated with increased levels of magnesium in am... |
Publication Detail:
|
Type: Editorial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-09-12 |
Journal Detail:
|
Title: American journal of physiology. Lung cellular and molecular physiology Volume: 295 ISSN: 1040-0605 ISO Abbreviation: Am. J. Physiol. Lung Cell Mol. Physiol. Publication Date: 2008 Dec |
Date Detail:
|
Created Date: 2008-12-02 Completed Date: 2009-01-22 Revised Date: 2013-06-05 |
Medline Journal Info:
|
Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: L979-87 Citation Subset: IM |
Affiliation:
|
Dept. of Pediatrics, Northwestern Univ. Feinberg School of Medicine, 303 E. Chicago Ave., Ward 12-196, Chicago, IL 60611, USA. k-farrow@northwestern.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Animals, Newborn Biopterin / analogs & derivatives, biosynthesis GTP Cyclohydrolase / biosynthesis Gene Expression Regulation, Enzymologic / drug effects* Humans Infant, Newborn Lung / enzymology* Nitric Oxide / metabolism Nitric Oxide Synthase Type III / biosynthesis* Oxidative Stress / drug effects Persistent Fetal Circulation Syndrome / drug therapy*, enzymology Pulmonary Artery / enzymology* Reactive Oxygen Species / metabolism Recombinant Proteins / pharmacology Respiration, Artificial Sheep Superoxide Dismutase / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
|
HL-086715/HL/NHLBI NIH HHS; HL-54705/HL/NHLBI NIH HHS; K08 HL086715-01/HL/NHLBI NIH HHS; R01 HL054705-12/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Reactive Oxygen Species; 0/Recombinant Proteins; 10102-43-9/Nitric Oxide; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.15.1.1/Superoxide Dismutase; EC 3.5.4.16/GTP Cyclohydrolase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Peroxynitrite augments fibroblast-mediated tissue remodeling via myofibroblast differentiation.
Next Document: Tryptase activates calcium-independent phospholipase A2 and releases PGE2 in airway epithelial cells...